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OLFACTORY TOXICITY RESULTING FROM DERMAL APPLICATION OF 2,6-DICHLOROBENZONITRILE (DICHLOBENIL) IN THE C57B1 MOUSE
Citation:
Deamer, N., J. O'Callaghan, AND M. Genter. OLFACTORY TOXICITY RESULTING FROM DERMAL APPLICATION OF 2,6-DICHLOROBENZONITRILE (DICHLOBENIL) IN THE C57B1 MOUSE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/092.
Description:
2,6-Dichlorobenzonitrile (dichlobenil) is an herbicide which has previously been reported by other investigators to be toxic to the olfactory mucosa following intraperitoneal administration. The objective of this study was to determine whether a more occupationally-relevant route of pesticide exposure, namely dermal exposure to dichlobenil, also resulted in olfactory system damage. Male C57B1 mice were clipped and administered 0-200 mg/kg dichlobenil dermally in acetone either as a single dose or for five consecutive days. In addition, olfactory bulb glial fibrillary acidic protein (GFAP) analysis was performed in order to determine whether the damage in the olfactory mucosa translated into damage which could be measured as an astroglial increase in GFAP concentration in the olfactory bulb, a marker of central nervous system neuronal loss. Olfactory mucosal histology revealed that single or multiple exposures to 50, 100, 150 and 200 mg/kg dichlobenil dermally caused olfactory epithelial damage (primarily sensory cell loss) in the epithelium lining the dorsal medial meatus of the nasal cavity. While the olfactory epithelial lesions were much less severe than those caused by i.p. administration of dichlobenil, GFAP was significantly elevated in both the 150 and 200 mg/kg treatment groups, demonstrating that relatively minor damage to a portion of the olfactory mucosa in the nasal cavity can be detected in the central nervous system.